A substituted indole nucleus is present in a variety of biologically active molecules including the important neurotransmitter serotonin, the potent hallucinogens psilocybin and LSD, the hypotensive and tranquilizer reserpine, and the CNS stimulant harmaline. The synthesis of these substituted indoles, their analogs, and their isotopically-labeled derivatives is often required for studies concerning their biochemical modes of action. The primary objectives of the proposed research are to develop a general and versatile strategy for the regiospecific synthesis of substituted indoles based upon our recently developed method involving the Meerwein arylation reaction of o-nitrophenyl diazonium salts with unsaturated acceptors, followed by reductive-cyclization; and to apply this strategy to the synthesis of a number of substituted indoles, including oxygenated indoles that have been utilized for the preparation of psychotropic indoles, and isotopically-labeled indoles that would be of value for biochemical studies. We have recently demonstrated the feasibility of this procedure in preliminary experiments in our laboratory.